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IMPORTANCE: Persistent hypothermia after cardiopulmonary bypass (CPB) in neonates with congenital heart defects (CHD) has been historically considered benign despite lack of evidence on its prognostic significance. OBJECTIVES: Examine associations between the magnitude and pattern of unintentional postoperative hypothermia and odds of complications in neonates with CHD undergoing CPB. DESIGN: Retrospective cohort study. SETTING: Single northeastern U.S., urban pediatric quaternary care center with an established cardiac surgery program. PARTICIPANTS: Population-based sample of neonates greater than or equal to 34 weeks gestation undergoing their first CPB between 2015 and 2019. INTERVENTIONS: None. MAIN OUTCOMES AND MEASUREMENTS: Hourly temperature measurements for the first 48 postoperative hours were extracted from inpatient medical records, and clinical characteristics and outcomes were accessed through the local patient registry. Group-based trajectory modeling (GBTM) identified latent temporal temperature trajectories. Associations of trajectories with outcomes were assessed using multivariable binary logistic regression. Outcomes (postoperative complications) were manually adjudicated by experts or were predefined by the patient registry. RESULTS: Four hundred fifty neonates met inclusion criteria. Their mean (sd) gestational age was 38 weeks (1.3), mean (sd) birth weight was 3.19 kilograms (0.55), median (interquartile range) surgical age was 4.7 days (3.3-7.0), 284 of 450 (63%) were male, and 272 of 450 (60%) were White. GBTM identified three distinct curvilinear temperature trajectories: persistent hypothermia (n = 38, 9%), resolving hypothermia (n = 233, 52%), and normothermia (n = 179, 40%). Compared with the normothermic group, those with persistent hypothermia had significantly higher odds of cardiac arrest, actionable arrhythmia, delayed first successful extubation, prolonged cardiac ICU length of stay, very poor weight gain, and 30-day hospital mortality. The persistent hypothermia group was characterized by greater odds of having a lower gestational age, more prevalent neurologic abnormalities, more unplanned reoperations, and a low surgical mortality risk assessment. CONCLUSIONS: Persistent postoperative hypothermia in neonates after CPB is independently associated with having greater odds of complications. Recovery patterns from postoperative hypothermia may be a clinically useful marker to identify patient instability in neonates. Additional research is needed for causal modeling and prospective validation before clinical adoption.
Assuntos
Ponte Cardiopulmonar , Cardiopatias Congênitas , Hipotermia , Complicações Pós-Operatórias , Humanos , Recém-Nascido , Estudos Retrospectivos , Ponte Cardiopulmonar/efeitos adversos , Masculino , Feminino , Hipotermia/etiologia , Hipotermia/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Cardiopatias Congênitas/cirurgia , Fatores de Risco , Estudos de CoortesRESUMO
Advanced brain imaging of neonatal macrostructure and microstructure, which has prognosticating importance, is more frequently being incorporated into multi-center trials of neonatal neuroprotection. Multicenter neuroimaging studies, designed to overcome small sample sized clinical cohorts, are essential but lead to increased technical variability. Few harmonization techniques have been developed for neonatal brain microstructural (diffusion tensor) analysis. The work presented here aims to remedy two common problems that exist with the current state of the art approaches: 1) variance in scanner and protocol in data collection can limit the researcher's ability to harmonize data acquired under different conditions or using different clinical populations. 2) The general lack of objective guidelines for dealing with anatomically abnormal anatomy and pathology. Often, subjects are excluded due to subjective criteria, or due to pathology that could be informative to the final analysis, leading to the loss of reproducibility and statistical power. This proves to be a barrier in the analysis of large multi-center studies and is a particularly salient problem given the relative scarcity of neonatal imaging data. We provide an objective, data-driven, and semi-automated neonatal processing pipeline designed to harmonize compartmentalized variant data acquired under different parameters. This is done by first implementing a search space reduction step of extracting the along-tract diffusivity values along each tract of interest, rather than performing whole-brain harmonization. This is followed by a data-driven outlier detection step, with the purpose of removing unwanted noise and outliers from the final harmonization. We then use an empirical Bayes harmonization algorithm performed at the along-tract level, with the output being a lower dimensional space but still spatially informative. After applying our pipeline to this large multi-site dataset of neonates and infants with congenital heart disease (n= 398 subjects recruited across 4 centers, with a total of n=763 MRI pre-operative/post-operative time points), we show that infants with single ventricle cardiac physiology demonstrate greater white matter microstructural alterations compared to infants with bi-ventricular heart disease, supporting what has previously been shown in literature. Our method is an open-source pipeline for delineating white matter tracts in subject space but provides the necessary modular components for performing atlas space analysis. As such, we validate and introduce Diffusion Imaging of Neonates by Group Organization (DINGO), a high-level, semi-automated framework that can facilitate harmonization of subject-space tractography generated from diffusion tensor imaging acquired across varying scanners, institutions, and clinical populations. Datasets acquired using varying protocols or cohorts are compartmentalized into subsets, where a cohort-specific template is generated, allowing for the propagation of the tractography mask set with higher spatial specificity. Taken together, this pipeline can reduce multi-scanner technical variability which can confound important biological variability in relation to neonatal brain microstructure.
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OBJECTIVE: To determine prevalence of and risk factors for infection in pediatric subjects with congenital heart disease status postcardiotomy supported on extracorporeal membrane oxygenation, as well as outcomes of these subjects. DESIGN: Retrospective cohort from the Extracorporeal Life Support Organization. SETTING: U.S. and international medical centers providing care to children with congenital heart disease status postcardiotomy. PATIENTS: Critically ill pediatric subjects less than 8 years old admitted to medical centers between January 1, 2013, and December 31, 2015, who underwent cardiac surgery for congenital heart disease and required extracorporeal membrane oxygenation support within the first 14 postoperative days. Subjects were excluded if they underwent orthotopic heart transplantation, required preoperative extracorporeal membrane oxygenation, and had more than one postoperative extracorporeal membrane oxygenation run. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 1,314 extracorporeal membrane oxygenation subject encounters in the Extracorporeal Life Support Organization registry met inclusion criteria. Neonates comprised 53% (n = 696) of the cohort, whereas infants made up 33% (n = 435). Of the 994 subjects with Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery categorizable surgery, 33% (n = 325) were in Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery category 4 and 23% (n = 231) in Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery category 5. While on extracorporeal membrane oxygenation, 229 subjects (17%) acquired one or more extracorporeal membrane oxygenation-related infections, which represents an occurrence rate of 67 infections per 1,000 extracorporeal membrane oxygenation days. Gram-negative (62%) and Gram-positive (42%) infections occurred most commonly. Forty percent had positive blood cultures. Infants and children were at higher infection risk compared with neonatal subjects; subjects undergoing less complex surgery had higher infection rates. Unadjusted survival to hospital discharge was lower in infected subjects compared with noninfected subjects (43% vs 51%; p = 0.01). After adjusting for confounders via propensity matching, we identified no significant mortality difference between infected and noninfected subjects. CONCLUSIONS: Neonatal and pediatric subjects in this study have a high rate of acquired infection. Infants and children were at higher infection risk compared with neonatal subjects. There was not, however, a significant association between extracorporeal membrane oxygenation-related infection and survival to hospital discharge after propensity matching.